Flower Buds Of Lonicera Japonica Research Articles

A Novel Caffeoylquinic Acid from Lonicera japonica Exerts Cytotoxic Activity by Blocking the YAP-CTGF Signaling Pathway in Hepatocellular Carcinoma

We have purified a novel caffeoylquinic acid named 3,4-di-O-caffeoylquinic acid isobutyl ester from the flower buds of Lonicera japonica Thunb., Caprifoliaceae. However, the biological function of 3,4-di-O-caffeoylquinic acid isobutyl ester is still unknown. Here, we found that 3,4-di-O-caffeoylquinic acid isobutyl ester effectively inhibited the proliferation and migration of hepatocellular carcinoma cells, and it displayed less toxicity to a normal liver cell line. Mechanistic studies showed that 3,4-di-O-caffeoylquinic acid isobutyl ester diminished the expression of YAP at the mRNA level. Overexpression of YAP significantly rescued HepG2 cells from the 3,4-di-O-caffeoylquinic acid isobutyl ester–induced suppression of proliferation and migration. Furthermore, the YAP downstream target gene CTGF was significantly repressed upon 3,4-di-O-caffeoylquinic acid isobutyl ester treatment, which was ameliorated by YAP overexpression. In addition, 3,4-di-O-caffeoylquinic acid isobutyl ester decreased the expression of β-catenin as well as CDK4/6. Collectively, 3,4-di-O-caffeoylquinic acid isobutyl ester exerts antihepatocellular carcinoma activity by inhibiting the YAP-CTGF pathway which controls the proliferation and migration of hepatocellular carcinoma cells. The Wnt/β-catenin pathway might be another pathway by which 3,4-di-O-caffeoylquinic acid isobutyl ester exerts antihepatocellular carcinoma activity. As a novel natural compound, 3,4-di-O-caffeoylquinic acid isobutyl ester might be a promising agent for hepatocellular carcinoma therapy.Graphical

Eugenol, Isolated from the Essential Oil from Lonicera japonica Flower Buds, Could Increase the Oxidative Stability of Sunflower Oil in the Deep-Frying Procedure of Youtiao

In order to assess the sunflower oil (SFO) oxidative stability that was added by the essential oils extracted from Lonicera japonica flower buds (LJEO) during deep-frying at 180 °C for 30 h, we clarified the compound/compounds of LJEO that improved the oxidative stability of SFO. The results displayed that the addition of LJEO (0.06 g/kg) could significantly restrict the elevation or the reduction in the levels of total polar compounds (TPC), thiobarbituric acid (TBA), conjugated dienes and conjugated trienes, and the values for polymer, viscosity and the color of SFO during the whole period. Meanwhile, the reduction in the sensory attributes, including flavor, taste, crispness and overall acceptability of the fried product, youtiao, was obviously restricted as well. After the bioassay-guided fractionation of LJEO and repeated deep-frying at 180 °C for 30 h, one of its chemical constituents, eugenol, was demonstrated to be the very compound that did significantly inhibit the oxidative rancidity of the SFO. Therefore, eugenol may be employed as potential effective natural antioxidants to inhibit the oxidative rancidity of SFO during its deep-frying procedures.

Annual dynamic variation of seven active components of Lonicera japonica in leaf growth and pruning periods

Pruning branches and leaves is the measure to stimulate the growth of Lonicera japonica flower buds, and consequently, the resources of pruned leaves are inevitably and seriously wasted in production. High-performance liquid chromatography(HPLC) was applied for content determination of seven active ingredients(chlorogenic acid, galuteolin, isochlorogenic acids A, B, and C, secologanic acid, and secoxyloganin) in L. japonica leaves from March to November. The results showed that the tillering removed from the trunk of L. japonica in March, the leaves pruned from May to July, and the leaves after the first frost date in November were rich in active ingredients, which deserved further exploitation and utilization. The total content(TC) of active ingredients in pruned L. japonica leaves in early March was the highest. The content of active ingredients in L. japonica leaves increased significantly after the first frost date, which was close to that in the bud tillers pruned in early and middle March. After the first frost date, L. japonica leaves are incapable of photosynthesis, and the harvesting of L. japonica leaves does not affect the physiological activities of the tree. In addition to huge resources, the content of active ingredients is high during this period, which is the best harvesting period of L. japonica leaves.

De novo transcriptomic analysis of light-induced flavonoid pathway, transcription factors in the flower buds of Lonicera japonica.

Key messageTranscriptomic analysis of the relationship between gene expression patterns and flavonoid contents in the flower buds of Lonicera japonica under light-induced conditions, especially the flavonoid pathway genes and transcription factors.Flos Lonicerae Japonicae (FLJ), the flower buds of Lonicera japonica Thunb., has been used to treat some human diseases including severe respiratory syndromes and hand-foot-and-mouth diseases owing to its putative antibacterial, and antiviral effects. Luteoloside is a flavonoid that is used by the Chinese Pharmacopoeia to evaluate the quality of FLJ. Light is an important environmental factor that affects flavonoid biosynthesis in the flower buds of L. japonica. However, how light triggers increases in flavonoid production remains unclear. To enhance our understanding of the mechanism involved in light-regulated flavonoid biosynthesis, we sequenced the transcriptomes of L. japonica exposed to three different light conditions: 100% light intensity (CK), 50% light intensity (LI50), and 25% light intensity (LI25) using an Illumina HiSeq 4000 System. A total of 77,297 unigenes with an average length of 809 bp were obtained. Among them, 43,334 unigenes (56.06%) could be matched to at least one biomolecular database. Additionally, 4188, 1545 and 1023 differentially expressed genes (DEGs) were identified by comparative transcriptomics LI25-vs-CK, LI50-vs-CK, and LI25-vs-LI50, respectively. Of note, genes known to be involved in flavonoid biosynthesis, such as 4-coumarate coenzyme A ligase (4CL), and chalcone synthase (CHS) were up-regulated. In addition, a total of 1649 transcription factors (TFs) were identified and divided into 58 TF families; 98 TFs exhibited highly dynamic changes in response to light intensity. Quantitative real-time PCR (qRT-PCR) was used to test the expression profiles of the RNA sequencing (RNA-Seq) data. This study offers insight into how transcriptional expression pattern is influenced by light in the flower buds of L. japonica, and will enhance the understanding of molecular mechanisms of flavonoid biosynthesis in response to light in L. japonica.Electronic supplementary materialThe online version of this article (10.1007/s00468-019-01916-4) contains supplementary material, which is available to authorized users.

A Simple, Rapid, and Practical Method for Distinguishing Lonicerae Japonicae Flos from Lonicerae Flos.

Lonicerae japonicae flos (LJF), the dried flower buds of Lonicera japonica Thunb., are often adulterated with Lonicerae. flos (LF), which is derived from the other four Lonicera species. Scholars at home and abroad have established several analytical methods to distinguish LJF from the four Lonicera species of LF; however, to date, no effective and practical method has been established for distinguishing LF from LJF. In our present study, the HPLC fingerprints of LJF and LF were compared, and differences in the content of one of the iridoids were found. Column chromatography combined with pre-HPLC was used for isolating and preparing the iridoid, and its structure was identified as secologanic acid. Then, a method for determining the content of secologanic acid was established using HPLC. The amounts of secologanic acid in 34 batches of LJF and 38 batches of LF were determined. The average amount of secologanic acid in 34 batches of LJF was 18.24 mg/g, with values ranging from 12.9 mg/g to 23.3 mg/g, whereas the average amount in 38 batches of LF was 1.76 mg/g, with values ranging from 0.2 mg/g to 7.2 mg/g. Therefore, secologanic acid can be considered as one of the characteristic components for distinguishing LJF and LF. Our study not only provides a rapid, simple, sensitive, and practical method for identifying LJF and LF but also establishes a method for discovering the characteristic components of other herb-medicines that are susceptible to adulteration.

Chemical constituents from Lonicera japonica flower buds and their anti-hepatoma and anti-HBV activities

Three new naturally occurring monoterpenoids, japopenoid A (1), japopenoid B (23) japopenoid C (24), and one new caffeoylquinic acid derivative (28), together with thirty-one known compounds (2–22, 25–27, 29–35), were isolated and identified from the flower buds of Lonicera japonica Thunb. Their structures were determined by extensive 1D and 2D NMR spectroscopic methods, high-resolution mass spectrometry, and the absolute configurations of 1, 23, 24 were determined by comparison of their electronic circular dichroism (ECD) spectrum with literature and theoretical calculation. Structurally, compound 1 is a monoterpenoid featured with an unusual tricyclic skeleton. All compounds (1–35) were evaluated for their cytotoxicities against human liver cancer cell lines (HepG 2 and SMMC-7721). Compound 12 exhibited the most potent activity with IC50 values of 26.54 ± 1.95 and 8.72 ± 1.57 μg/ml against HepG 2 and SMMC-7721, and the IC50 values of compound 13 were 26.54 ± 1.95 and 12.35 ± 1.43 μg/ml, respectively. Western blot results further proved that compound 13 induces hepatoma cell apoptosis via the intrinsic apoptosis pathway. In addition, most terpenoids showed inhibitory activity against HBsAg and HBeAg secretion, and HBV DNA replication. In particular, 25 μg/mlof compound 11 inhibits HBsAg and HBeAg secretion, and HBV DNA replication by 39.39 ± 5.25, 15.64 ± 1.25, and 16.13 ± 4.10% compared to the control (p < 0.05). These results indicated that L. japonica flower buds could be served as functional food for anti-hepatoma and anti-HBV activities.

Effects of a novel biflavonoid of Lonicera japonica flower buds on modulating apoptosis under different oxidative conditions in hepatoma cells

Background: In our previous work, we purified a novel biflavonoid named Japoflavone D (JFD) from Lonicera japonica flower buds. Biflavonoids are chemical compounds characterized by their high levels of antioxidative activity. PurposeThe present study aimed to investigate the function and molecular mechanism of JFD under different oxidative conditions in hepatoma cells. MethodsMTT assay and apoptosis assay were used to evaluate the cytotoxic effect of JFD. The activities of SOD and CAT were detected to evaluate the oxidative level. Oxidative stress was induced by H2O2 stimulation. The molecular mechanism of JFD was investigated by analyzing relative signaling pathway. ResultsJFD inhibited cell viability in all hepatoma cell lines we examined. Under quiescent conditions, JFD treatment of SMMC-7721 cells resulted in upregulation of AKT/mTOR signal pathway and ERK activities and downregulation of KEAP1/NRF2/ARE signaling axis, together with apoptosis. However, under oxidative stress, JFD played a quite different role. Treatment of JFD suppressed the activation of ERK and mTOR and activated the KEAP1/NRF2/ARE signaling axis, which is a predominant regulator of cytoprotective responses to oxidative stress, thereby lessening the damage caused by excess reactive oxygen species (ROS). A molecular docking analysis suggested that JFD may interrupt the interaction between KEAP1 and NRF2 by competitively anchoring to the NRF2 binding site on KEAP1. ConclusionThe results indicate that JFD functions as a potent antioxidant and plays dual roles in modulating apoptosis under different oxidative conditions. JFD has the potential to be developed as a protective drug for diseases related with excess ROS.

A new constituent against rheumatoid arthritis from the flower buds of Lonicera japonica

In this study, two new compounds named as 8,4′-di-O-methylquercetin-3′-O-β-galactosyl-3-O-β-glucopyranoside (1) and 6-formyl-5-hydroxyl-4-ethyl-2-hydroxymethyl-1H-indene (2), were isolated from the flower buds of Lonicera japonica. Structures of compound 1 and 2 were determined by spectroscopic methods. Additionally, compound 1 showed therapeutic effects against rheumatoid arthritis (RA) in collagen-induced arthritis (CIA) mice through significantly reducing the inflammatory responses in the joint tissues. These results suggested that compound 1 exerted potent chondroprotective and anti-inflammatory effects against RA.

Novel flavonoids from Lonicera japonica flower buds and validation of their anti-hepatoma and hepatoprotective activity in vitro studies

Lonicera japonica, a widely used traditional Chinese medicine, possessed antiviral, hepatoprotective, anti-tumor and other activities. Meanwhile, L. japonica could be used as healthy food, cosmetics, and so on. Herein, four novel flavonoids, japoflavone A–D (2-3, 5, 12), together with ten known flavonoids, were isolated and identified on the basis of spectroscopic evidence from L. japonica. In addition, all isolates were assayed for their anti-hepatoma and hepatoprotective activities in vitro. 5 and 8 showed significant anti-hepatoma activity in SMCC 7721 cell with IC50 values of 13.01 ± 2.62 and 16.69 ± 0.35 μg/ml; Compound 12 showed significant hepatoprotective activity against H2O2-induced injury in SMCC 7721 and HepG 2 cells (p < 0.001). Drop in the levels of catalase and superoxide dismutase caused by H2O2 were remarkably reversed in a dose-dependent manner after treatment with 12. This study provided a phytochemical evidence for further development and utilization of Lonicera japonica in health products.

Large-scale purification of unstable, water-soluble secologanic acid using centrifugal partition chromatography.

Secologanic acid, a major secoiridoid in the flower buds of Lonicera japonica, is a fragile, highly polar compound that readily changes to epivogeloside or vogeloside after being dissolved in methanol. Thus, it is very difficult to obtain secologanic acid on a large-scale. To develop a centrifugal partition chromatography (CPC) method for large-scale purification of secologanic acid with high purity from the flower buds of L. japonica. After fractionation with Diaion HP-20 macroporous resin, 30% methanol eluent was purified by CPC with a ternary biphasic solvent system with ethyl acetate/isopropanol/water (6:4:10, v/v/v). CPC was performed separately twice with the same solvent system, first in descending mode and second in ascending mode. After the first CPC operation, a secologanic acid enriched fraction (586mg) was obtained from 3g of crude extract, and secologanic acid (206mg) was isolated with a purity over 93% in the subsequent ascending mode with the same solvent system from a 586mg enriched fraction. In addition, it was confirmed that epivogeloside and vogeloside were reversely converted to secologanic acid in an aqueous acidic solution. These results demonstrate that CPC is a simple, effective, and rapid method for the purification of secologanic acid in the flower buds of L. japonica.

A new dimeric secoiridoids derivative, japonicaside E, from the flower buds of Lonicera japonica

A new dimeric secoiridoids derivative, named japonicaside E, together with six known compounds were isolated from the flower buds of Lonicera japonica. The structures of these compounds were elucidated by the analyses of mass spectrometry and NMR spectroscopy. All compounds were evaluated for anti-inflammatory activity in vitro.

Two thymol derivatives from the flower buds of Lonicera japonica and their antibacterial activity

A new monoterpenoid, 7-acetyl-8,9-dihydroxy thymol (1), together with a known one 7,8-dihydroxy-9-buyryl thymol (2), were isolated from the dried flower buds of Lonicera japonica Thunb. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses. The potential antibacterial effects of these compounds on Staphylococcus aureus, Escherichia coli, Micrococcus luteus, and Bacillus cereus were evaluated. Interestingly, both compounds 1 and 2 exhibited significant antibacterial activities with IC50 values range from 27.64 ± 2.26 to 128.58 ± 13.26 μg/mL.

Isolation and functional characterization of a Lonicera japonica hydroxycinnamoyl transferase involved in chlorogenic acid synthesis

AbstractThe flower buds of

Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of Lonicera japonica in streptozotocin-induced diabetic rats

Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM). In this study, one fraction of the crude polysaccharides extracted from Lonicera japonica flower buds (LJP) were investigated for its hypolipidaemic and hypoglycaemic activities by means of streptozotocin (STZ)-induced diabetic rats. Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP for 42 days, the food and water intake and the levels of sugar and insulin in blood for the diabetic rats were drastically decreased, while the contents of liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate kinase and hexokinase were obviously increased (p<0.01 or p<0.05). The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterin (LDL-C) and very-low-density lipoprotein-cholesterin (VLDL-C) were significantly descended, while high-density lipoprotein-cholesterin (HDL-C) was significantly ascended (p<0.01 or p<0.05). In addition, the oxidant stress in liver was restored as well. The results suggested that LJP could be considered as an ingredient of functional foods for diabetes, and this is the first report about the hypoglycemic and hypolipidemic effects of the polysaccharides extracted from Lonicera japonica.

Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection.

ReDuNing injection, prepared from a combination of Gardenia Jasminoides fruits, Lonicera japonica flower buds, and the Artemisia annua aerial part, is extensively used for treatment of viral upper respiratory tract infections in China. Iridoids, organic acids, and flavonoids are likely important compounds of the herbal injection because of their reported pharmacological properties. This study was designed to characterize pharmacokinetics and disposition of the major circulating herbal compounds in rats that received the injection intravenously. ReDuNing injection was found to contain 19 iridoids (content levels 0.01-27.93 mM), 16 organic acids (0.04-19.06 mM), and 11 flavonoids (<0.08 mM). After dosing the injection, the iridoids geniposide, secologanic acid, secoxyloganin, genipin-1-β-gentiobioside, geniposidic acid, sweroside, and shanzhiside and the organic acids chlorogenic acid, quinic acid, cryptochlorogenic acid, and neochlorogenic acid were found to be the major circulating compounds, with mean elimination half-lives of 0.2-0.9 hour; the other plasma compounds were at low exposure levels. These major circulating compounds exhibited small apparent volumes of distribution (0.03-0.34 l/kg). Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds, whereas the organic acids were eliminated via methylation and sulfation and were excreted into urine as the unchanged and metabolized compounds. The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion. In vitro data suggested that the metabolism of the organic acids in rats also occurred in humans. The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.

A new hetero dimeric terpenoid derivative, japonicaside C, from the flower buds of Lonicera japonica

A rare hetero dimeric terpenoid derivative, named japonicaside C, together with five known secoiridoid gloucosides were isolated from the flower buds of Lonicera japonica. The structures of these compounds were established on the basis of spectroscopic analyses. Japonicaside C is the first representative of a novel type of hetero dimeric terpenoid, biogenetically originated from a guaiane-type sesquiterpenoid and a secoiridoid glucoside. Anti-virus activity of the isolated compounds was evaluated in vitro.

Anti-encystment and amoebicidal activity of Lonicera japonica Thunb. and its major constituent chlorogenic acid invitro.

To examine the acanthamoebicidal effects of ethyl acetate, aqueous and butanol fractions of dried flower buds of Lonicera japonica (L. japonica) Thunb. (Flos Lonicerae) invitro. Acanthamoeba triangularis isolates were obtained from environmental water samples and identified by PCR. They were exposed to ethyl acetate, water and butanol fractions of L.japonica Thunb. at concentrations ranging from 0.5mg/mL to 1.5mg/mL. The extracts were evaluated for growth inhibition at 24, 48 and 72h, respectively. Chlorogenic acid at a concentration of 1mg/mL was examined for inhibition of encystment. Ethyl acetate fraction at a concentration of 1.5mg/mL evoked a significant reduction of trophozoite viability by 48.9% after 24h, 49.2% after 48h and 33.7% after 72h chlorogenic acid, the major active constituent of L.japonica Thunb. at the concentration of 1mg/mL reduced the cysts/trophozoite ratio by 100% after 24h, 84.0% after 48h and 72.3% after 72h. This phenolic compound at concentration of 1mg/mL concurrent with 0.6% hydrogen peroxide inhibited hydrogen peroxide-induced encystment by 92.8% at 72h. Results obtained from this study show that ethyl acetate fraction at 1.5mg/mL is the most potent fraction of L.japonica Thunb. and its major constituent chlorogenic acid showed the remarkable inhibition of encystment at a concentration of 1mg/mL.

Secondary metabolites from the flower buds of Lonicera japonica and their in vitro anti-diabetic activities

Four new compounds (1, 2, 7 and 8) and twenty known compounds were isolated from the flower buds of Lonicera japonica. Their structures were determined by extensive NMR and HR-ESIMS spectroscopic data analyses. Among them, compounds 1 and 2 are a pair of diastereoisomers possessing a rare chemical structure, and their absolute configurations were determined by comparing their experimental and calculated ECD spectra. Furthermore, all the isolates were evaluated for their inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), especially 1 and 2, which displayed both significant inhibitions. In addition, the possible action mechanism of the active compounds was also explored by using molecular docking studies.

Protective Effect of Flowerbuds of Lonicera Japonica Extract on Diabetes Mellitus Type 2 and Associated Vascular Complications in STZ-HFD Treated Rats

Objective : To study the protective effect of Lonicera Japonica Alcoholic Extract (LJALE) on Diabetes Mellitus II (DM) and associated vascular complications. Methods : Induction of Diabetes Mellitus II with 35 mg / kg STZ-HFD leads to excessive level of 11β-HSD1 enzyme. It has been found that flower buds of Lonicera Japonica (LJ) has also been traditionally indicated for treatment of diabetes. Chlorogenic Acid (CA) is a major bioactive component in the flower buds of LJ has received more attention because of its 11β-HSD1 inhibitory action.11β-HSD1 regulates glucocorticoid action at the pre-receptor stage by converting cortisone to cortisol. Elevated glucocorticoids are a key risk factor for metabolic diseases. LJALE was prepared with help of Microwave Assisted Extraction (MAE) method. STZ-HFD-induced diabetic rats were treated with LJALE (200 mg/kg, 500 mg/kg) and Metformin (50 mg/kg). It was given for 4 weeks. Result: LJALE treated Diabetic rats showed significant decreased in blood glucose levels, plasma insulin, serum cortisol as well significant increased hepatic glycogen, 11β-HSD1 index compare to diabetic control rats. LJALE (500 mg/kg) treatment showed the return of islets close to good vascular pattern. LJALE treatment restored endothelium dysfunction. Conclusions: From all results it is reasonable to conclude that LJALE (500 mg/kg) may be used in treatment of diabetes and diabetes associated vascular dysfunction. Keywords: Diabetes Mellitus, 11β-HSD1, CA, LJALE

Gout prophylactic constituents from the flower buds of Lonicera japonica

Two new sesquiterpene glycosides (R)-dehydroxyabscisic alcohol β-d-apiofuranosyl-(1″→6′)-β-d-glucopyranoside (1) and (−)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hydroxy methyltricyclic[5.3.1.02,6]-undec-8-en-10-one β-d-apiofuranosyl-(1″→6′)-β-d-glucopyranoside (2), were isolated from the flower buds of Lonicera japonica. Their structures were determined by spectroscopic and chemical methods. Compound 2 could significantly decrease monosodium urate-mediated cytokine production from activated macrophage through lowering IL-1β and TNFα.